4BID

Crystal Structures of Ask1-inhibitor Complexes

4BID の概要

• エントリーDOI: 10.2210/pdb4bid/pdb
• 関連するPDBエントリー: 4BF2 4BHN 4BIB 4BIC 4BIE
• 分子名称: MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 5, ACETATE ION, 5-[(1R)-2-amino-1-phenylethoxy]-2-(furan-3-yl)-3-{1H-pyrrolo[2,3-b]pyridin-3-yl}pyridine, ... (4 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q99683
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71987.77

構造登録者

Singh, O.,Shillings, A.,Craggs, P.,Wall, I.,Rowland, P.,Skarzynski, T.,Hobbs, C.I.,Hardwick, P.,Tanner, R.,Blunt, M.,Witty, D.R.,Smith, K.J. (登録日: 2013-04-10, 公開日: 2013-07-03, 最終更新日: 2023-12-20)

主引用文献

Singh, O.,Shillings, A.,Craggs, P.,Wall, I.,Rowland, P.,Skarzynski, T.,Hobbs, C.I.,Hardwick, P.,Tanner, R.,Blunt, M.,Witty, D.R.,Smith, K.J.
Crystal Structures of Ask1-Inhibtor Complexes Provide a Platform for Structure Based Drug Design.
Protein Sci., 22:1071-, 2013

PubMed Abstract: ASK1, a member of the MAPK Kinase Kinase family of proteins has been shown to play a key role in cancer, neurodegeneration and cardiovascular diseases and is emerging as a possible drug target. Here we describe a 'replacement-soaking' method that has enabled the high-throughput X-ray structure determination of ASK1/ligand complexes. Comparison of the X-ray structures of five ASK1/ligand complexes from 3 different chemotypes illustrates that the ASK1 ATP binding site is able to accommodate a range of chemical diversity and different binding modes. The replacement-soaking system is also able to tolerate some protein flexibility. This crystal system provides a robust platform for ASK1/ligand structure determination and future structure based drug design.

PubMed: 23776076
DOI: 10.1002/PRO.2298

実験手法

X-RAY DIFFRACTION (2.8 Å)